The goal of this project is to evaluate the involvement of activated macrophages macrophages as effector cells of immunity to infection by the helminth parasite, Schistosoma mansoni. Three mouse models of resistance are being explored in this study: (1)"concomitant immunity" i.e., the partial resistance to challenge S. mansoni infection that develops as a consequence of ongoing primary infection, (2) BCG-induced resistance, and (3) vaccination with highly irradiated S. mansoni cercariae. In each of these models macrophages activated for in vitro killing of extracellular targets (tumor cells, skin-stage schistosomula) can be elicited. Production of macrophage activating factors after specific antigen challenge of S. mansoni-infected or vaccinated mice in vivo or of lymphoid cells from these mice in vitro has been observed. When development of S. mansoni-induced (concomitant immunity model) was examined in several inbred strains of mice previously characterized as displaying defective macrophage activation for tumor cytotoxicity after BCG infection in vivo, a correlation was observed between macrophage activity and resistance to challenge infection. These studies suggest that activated macrophages may play a role in immunity to this parasite.